The WHO has targeted malaria amongst the five most devastating diseases worldwide. Malaria accounts for over 600 million new cases and more than 2 million deaths annually. The most dangerous species of parasite causing malaria is Plasmodium falciparum. This species may cause neurovascular involvement leading to coma and death. The life cycle of this parasite is complex. It includes various parasite forms in the arthropod vector, the mosquito, as well as liver (exoerythrocytic) and blood (erythrocytic) forms of the parasite in the human host. During blood stage development the pathway proceeds from ring to trophozoite to schizont, and finally to individual merozoites which initiate the next round of infection of red blood cells. During this asexual blood stage cycle, some of the ring stage parasites differentiate into sexual forms. Male (micro) and female (macro) gametocytes are the only forms of the malaria blood stage parasite capable of resulting in infection of the mosquito, thus completing the entire life cycle. Little is known about the initiation of gametocytogenesis, in particular the molecular events responsible for the switch from asexual blood stage development to sexual blood stage development. There still appears to be disagreement on when during asexual blood stage development the switch occurs and whether cyclic nucleotides play a role in the signalling. Recently, we have initiated studies to identify classes of transcription factors which are known in other biological systems (e.g. C. elegans, drosophila, and mouse) to be involved in differentiation. The expectation is that these transcription factors are evolutionarily conserved in structure and function. Understanding the regulatory events responsible for stage differentiation may provide further insight into disrupting the normal life cycle of this deadly parasite.